Phospholipids make a vital contribution to the characteristic permeability of cells. It has become apparent that quantitative, and even qualitative, changes of their content in cell membranes can influence the movement of molecules between the cell and its environment. Recently, we have found that a phospholipase enzyme can specifically increase the permeability of two "model" epithelial membranes to sodium. An endogenous phospholipase (A2) has been isolated from rabbit kidney, frog skin and toad urinary bladder. The relationship between phospholipase activation and the antidiuretic hormone (ADH) effect is being investigated. As phospholipase A2 is the rate limiting step in the formation of prostaglandins (PG) we are in the process of identifying prostaglandins released from prelabelled membrane phospholipids in response to ADH as well as aldosterone utilizing RIA and bioassay. The further purification and characterization of the kidney phospholipase continues with emphasis on substrate specificity, product formation and the role of calcium and the calcium regulatory protein in the phospholipase -prostaglandin biosynthetic cascade. These studies may provide important information about the mechanism involved in hormonal control of renal fluid and electrolytes and may have practical implications in the diagnosis and treatment of diseases that affect the kidney and the design of drugs that modify its function.